Field of the Invention
The present invention relates to a composition for muscle function improvement or exercise ability enhancement, the composition including kirenol, a Siegesbeckia herba extract, or a fraction of the Siegesbeckia herba extract as an active ingredient.
Discussion of Related Art
It has been known that the decline in human physical activity over the past 50 to 100 years is associated with a growing incidence of metabolic diseases such as type 2 diabetes, obesity, and cardiovascular diseases. Lack of physical activity is the fourth leading cause of death as reported by the World Health Organization. For this reason, organizations such as the World Health Organization, the American Heart Association, and the British Heart Foundation recommend a minimum of 30 minutes of aerobic exercise for at least five days a week. In fact, exercise reduces the incidence of diabetes, obesity, breast cancer, and colorectal cancer, and has a good therapeutic effect on depression (Br. J. Pharmacol. 170:1153-1166, 2013, Am. J. Cardiol. 110: 58B-68B, 2012).
One of the representative methods for improving exercise ability by promoting energy consumption is to increase fatty acid oxidation by mitochondria to produce adenosine triphosphate (ATP) energy. It has been discovered that the number and performance of the regulating mitochondria is controlled by a coactivator referred to as peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α), and that PGC-1α activity is regulated by SIRT1 (sirtuin 1) (EMBO. J. 26: 1913-1923, 2007, Cell Metab. 1: 361-370, 2005).
Scarpulla and his co-workers identified proteins known as nuclear respiratory factors (NRFs) (J. Cell. Biochem. 97: 673-683, 2006). Proteins of the NRF family activate the replication and transcription in mitochondria by binding to promoters of various genes in the nucleus. It has been discovered that the production of mitochondria is induced by activated mitochondrial replication and transcription. Also, it has been found that the expression of proteins of the NRF family is enhanced as the proteins physically interact with PGC-1α (Cell 98:115-24, 1999).
In addition, AMPK, p-AMPK, PPARδ, ERRα, Tfam, and the like are known as factors associated with exercise ability enhancement.
Meanwhile, muscle atrophy refers to muscle weakness and muscle degeneration and is caused by a gradual decrease in muscle mass (Cell 119: 90710, 2004). Muscle atrophy is accelerated by lack of activity, oxidative stress, and chronic inflammation, and weakens muscle function and exercise ability (Clin. Nutr. 26: 524-534, 2007). Muscle mass is the most important determinant of muscle functions and is maintained by the balance between protein synthesis and protein degradation. Muscle atrophy occurs when protein degradation exceeds protein synthesis (Cell Biol. 37: 1985-1996, 2005).
Muscle size is regulated by intracellular signaling pathways that induce anabolism or catabolism within muscle. When signals inducing muscle protein synthesis exceed signals inducing muscle protein degradation, more muscle proteins are synthesized. An increase in muscle protein synthesis results in an increase in muscle size (hypertrophy) or an increase in the number of muscle fibers (hyperplasia) due to an increase in the amount of muscle proteins (The Korea Journal of Sports Science 30: 1551-1561, 2011).
Factors inducing hypertrophy induce protein synthesis by phosphorylating downstream proteins upon the stimulation of phosphatidylinositol-3 kinase (PI3K)/Akt pathways in muscle cells. Among the factors, the activation of mechanistic target of rapamycin (mTOR) due to PI3K/Akt signaling is recognized as a main growth signaling mechanism that integrates various growth signals in cells. The activation of mTOR contributes to an increase in the muscle mass by inducing muscle protein synthesis through the activation of 4E-binding protein 1 (4E-BP1) and phosphorylated 70-kDa ribosomal S6 kinase (p70S6K), both of which are downstream targets (The Korea Journal of Sports Science 30: 1551-1561, 2011, J Biol Chem 278:40717-40722, 2003).
Muscle cell differentiation and muscle formation are regulated by various muscle regulatory factors (Cell Mol Life Sci 70: 4117-4130, 2013). Among the factors, MyoD initiates the expression of genes specific for muscle differentiation and induces mesenchymal stem cells to differentiate into myoblasts. Myogenin, which is regulated by MyoD, is the most important factor in the fusion of myoblasts, and is involved with the formation of myotubes. The muscle fibers formed through the above process form a bundle and eventually form muscles (Cell Mol Life Sci 70: 4117-4130, 2013; Sci Signal 6: re2, 2013).
Siegesbeckia herba is the dried aerial part of Siegesbeckia glabrescens Mak., Siegesbeckia pubescens Mak., or Siegesbeckia orientalis L., all of which are Siegesbeckia spp. and members of the genus Siegesbeckia and the family Asteraceae. Siegesbeckia glabrescens Mak., also known as Jindeukchal in Korea, is reported to exhibit antimicrobial (Int. J. Food Microbiol. 160: 260-266, 2013), anticancer (Oncol. Rep. 30: 221-226, 2013), antidiabetic (J. Enzyme Inhib. Med. Chem. 21: 379-383, 2006), anti-inflammatory (Food Agric. Immunol. 22: 145-160, 2011) activities, and the like. Siegesbeckia pubescens Mak., also known as Teoljindeukchal in Korea, is reported to exhibit anti-inflammatory and analgesic (Pak. J. Pharm. Sci. 21: 89-91, 2008), antioxidant and anti-obesity (Kor. J. Microbiol. Biotechnol. 41: 341-349, 2013), wound healing (J. Ethnopharmacol. 134: 1033-1038, 2011), arthritis treatment (Phytomedicine 19: 882-889, 2012) activities, and the like. Siegesbeckia orientalis L., also known as Jejujindeukchal in Korea, is reported to exhibit anticancer (Natural Product Radiance 6: 34-39, 2007), anti-inflammatory (Chem. Biodivers. 3: 754-761, 2006), antioxidant (Korean J. Pharmacogn. 36: 150-163, 2005) activities, and the like.
Kirenol is a diterpenoid mainly found in Siegesbeckia herba and is reported to exhibit anti-inflammatory and analgesic effects (J. Ethnopharmacol. 137: 1089-1094, 2011), an antimicrobial effect (Pharmacogn. Mag. 8: 149-155, 2012), an arthritis treatment effect (Phytomedicine 19: 882-889, 2012), an anti-obesity effect (BBRC 445, 433-438, 2014), and the like.
However, prior to the present invention, there has been no report on the effect of Siegesbeckia herba or kirenol in terms of muscle function improvement or exercise ability enhancement.